The development, biosynthesis and degradation, maturation and assembly, and regulation of catalytic efficiency of rat lung metalloenzymes will be studied in vivo and in vitro. The role of the respective metal cofactors in regulation of and involvement in these processes will be elucidated. The mechanism by which environmental toxic metals, such as cadmium, tungsten, vanadium, and zinc, interfere with and disrupt these prcesses will be examined. In addition the effects of different environmental gases, such as O2, O3, SO2, and NO2, on these processes for metalloenzymes will be examined. In particular the following enzymes will be monitored: superoxide dismutase (copper, zinc, manganese), sulfite oxidase (molybdenum, heme), cytochrome oxidase (copper, heme), xanthine oxidase (molybdenum, iron) and possibly ceruloplasmin (copper). The role of the metal cofactor will be studied by growing newborn rats under conditions of specific dietary metal deprivation. The effects of environmental toxic metals on metalloenzymes will be determined in two ways: by dietary administration of these metals, and by inhalation of aerosol dispersed metals. Finally, by growing newborn and adult rats in a gas tight chamber, the effects of environmental gases on the metalloenzymes involved in their metabolism, e.g., sulfite oxidase, superoxide dismutase, and cytochrome oxidase, can be monitored. Development of metalloenzymes will be observed by following the appearance of enzymic activity as a function of the age of the rat. Biosynthesis and degradation will be studied by determination of the rates of these processes using the double isotope technique (R.T. Schimke and D. Doyle (1970) Ann. Rev. Biochem., 39, 929-976). Maturation and assembly will be studied in vitro monitoring formation of apoenzyme from subunits and holoenzyme from apoenzyme and the metal cofactor. Regulation of catalytic efficiency will be observed using toxic metals as inhibitors and antagonists and gases as inhibitors.